Effects of An Omega‐3 High‐Fat Diet on Skeletal Muscle Protein Degradation in Glucocorticoid‐Induced Muscle Wasting

Abstract

Treatment with synthetic glucocorticoids induces muscle atrophy and are commonly used in the treatment of a variety of inflammatory and autoimmune diseases. Omega‐3 (n‐3) polyunsaturated fatty acids elicit beneficial effects in several muscle atrophy conditions. Therefore, the purpose of this study was to determine if a high‐fat diet rich in n‐3 is protective of glucocorticoid‐induced protein degradation. Male wild type C57BL/6 mice were randomized into two groups: n‐6 (45% fat 177.5 g lard) and n‐3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of 3 mg/kg/day dexamethasone (Dex) or sterile phosphate buffered saline, for 1 week while continuing diets. At sacrifice the gastrocnemius muscle was weighed and dissected into red and white portions before being snap frozen and processed for RNA extraction and protein extraction. Dex reduced gastrocnemius weight by 12% independently of diet. Protein degradation signaling in the white gastrocnemius was altered by Dex with increased atrogin‐1 expression (p=0.004) without a change in muscle RING finger 1 (MuRF‐1) expression (p=0.15). There was a large effect of Dex to decreased phosphorylation of forkhead box transcription factor O3a (FOXO3a) (Cohen’s d=1.42), increased phosphorylation of glycogen synthase kinase 3β (GSK‐3β) (Cohen’s d=1.42). However, the negative effects of dexamethasone were not attenuated by an n‐3 high‐fat diet. There was no effect of Dex or diet on phosphorylation of FOXO3a (p=0.17) or GSK3β (p=0.60) in red gastrocnemius muscle. These data support the detrimental effects of dexamethasone on muscle atrophy and report no benefit of an n‐3 high‐fat diet.Support or Funding InformationFunding provided by University of Memphis School of Health Studies